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Biomedical subjects

S Ledoux

Publications and source records attributed to S Ledoux.

At least 37 records · Page 2Linked to original sources
PubMed1997

Increased expression of the peripheral-type benzodiazepine receptor-isoquinoline carboxamide binding protein mRNA in brain following portacaval anastomosis.

Using RT-PCR, gene expression of the peripheral-type benzodiazepine receptor isoquinoline carboxamide-binding protein (PTBR-IBP) was studied in the frontal cortex of rats four weeks following end-to-side portacaval anastomosis, an experimental animal model of hepatic encephalopathy, or sham operation. Portacaval anastomosis resulted in increased expression of PTBR-IBP in frontal cortex and in a concomitant increase in densities (Bmax) of binding sites for the PTBR ligand [3H]PK11195. In view of the findings that the PTBR modulates the synthesis of neurosteroids with high affinity for excitatory and inhibitory neurotransmitter systems in brain, increased expression of these receptors could be implicated in the pathogenesis of hepatic encephalopathy.

Animals↗
PubMed1997

Psychosocial factors associated with help-seeking behavior among depressive adolescents.

A group of 3,287 French school pupils between the age of 12 to 20 years, of whom 14.4% had sought consultation for depression, were investigated in order to analyse the factors related to the type of medical help obtained. Multivariate analyses showed that severe emotional distress alone did not explain the help-seeking behavior. Thus, among those adolescents with the same anxio-depressive level, girls, older adolescents, adolescents with parents living apart, with health worries, and adolescents often absent from school more often sought help for depression. Socio economic status, however, did not correlate with a higher level of consultation for depression. Adolescents attending medical services for depression had a higher consultation rate, for any reason, with general practitioners and with school nurses, in whom they confided more often than their counterparts. Nonmedical professionals also seemed to contribute to accessing to medical help for depression. Overall, those who consulted for depression, in very limited numbers turned to mental health services (8.4%).

Adolescent↗
PubMed1997

Self-reported health and behavioral problems among adolescent victims of rape in France: results of a cross-sectional survey.

OBJECTIVES: To measure the prevalence rate of rape among French adolescents; to analyze the associated health and behavioral problems; to analyze the use of the health care system by rape victims. METHOD: A national representative sample of 8,140 students attending public secondary schools in France (grades 8 to 12) filled in a self-administered questionnaire (274 questions) on health and behavior problems (acceptance rate = 87%). Each rape victim in the sample (n = 61) was matched to two nonvictims (n = 122). RESULTS: The reported prevalence rate of rape was .8% (.9% among girls, .6% among boys). For both boys and girls, there was a relationship between rape and current sleep difficulties, depressive symptoms, somatic complaints, tobacco consumption, and behavior problems (running away, violent behavior, stealing, and school absenteeism). Additional problems were associated for boy rape victims: attempted suicide, regular use of alcohol and of illicit drugs. Rape victims did consult health professionals, but the majority saw neither a mental health specialist nor a social worker. CONCLUSION: The findings indicate that rape victims, especially boys, have more behavior problems and health problems than nonrape victims. Authors suggest that adolescents who have ran away from home, attempted suicide, or manifested violent behavior should be systematically asked about rape.

Adolescent↗
PubMed1997

Overexpression of ecto-5'-nucleotidase promotes P-glycoprotein expression in renal epithelial cells.

UNLABELLED: P-glycoprotein (P-gp), responsible for multidrug resistance (MDR) of tumoral cells, is also expressed in apical membranes of normal epithelial cells, among which are proximal tubular cells. Ecto-5'-nucleotidase (5'Nu), co-located with P-gp in renal brush border membranes, could be instrumental in the expression of MDR phenotype. P-gp activity [assessed by rhodamine 123 (R123) and [3H]vinblastine (3H-VBL) accumulation] was evaluated in MDCK cell lines in which human 5'Nu was expressed at different levels after retroviral infection: MDCK-5'NU/- cells with a low 5'Nu activity (Vmax < 2 pmol/mg protein/min) and MDCK-5'NU/+ cells, which expressed a high level of 5'Nu (Vmax 150 +/- 18.5 pmol/mg protein/min). MDCK-5'NU/- cells did not display functional expression of MDR. In MDCK-5'NU/+ cells, R123 and 3H-VBL accumulation was significantly lower than in MDCK-5'NU/- cells and was dramatically enhanced by P-gp inhibitors. This high P-gp activity in MDCK-5'NU/+ cells was confirmed by their resistance to colchicine (measured by LDH release and MTT assay) as compared to MDCK-5'NU/- and was accounted for by increased membrane expression of P-gp assessed by Western blot. Neither AMP nor adenosine, the substrate and the product of 5'Nu, respectively, affected P-gp activity. Inhibition of 5'Nu with alpha beta-methylene-adenosine-diphosphate (alpha beta MADP) or with a blocking anti-5'Nu antibody (1E9) did not blunt MDR expression in MDCK-5'NU/+ cells. Conversely, the anti-5'Nu antibody 5F/F9, which did not block the enzymatic site, induced a decrease of P-gp activity. Further, incubation of MDCK-5'NU/- cells with conditioned medium from MDCK-5'NU/+ cells, which contained significant amounts of released 5'Nu, induced MDR phenotype. IN CONCLUSION: (i) expression of ecto-5'Nu promotes multidrug resistance (MDR) activity in renal epithelial cells by enhancement of P-gp expression; (ii) this effect does not involve enzymatic activity of 5'Nu; (iii) supernatants of cells that express 5'Nu conferred P-gp activity to 5'Nu negative cells.

5'-Nucleotidase↗
PubMed1997

Protein kinase A activity modulates natriuretic peptide-dependent cGMP accumulation in renal cells.

The purpose of this work was to examine whether the level of cAMP accumulation and protein kinase A (PKA) activity influence atrial natriuretic factor (ANF)-dependent guanosine 3',5'-cyclic monophosphate (cGMP) production in two renal cell types: rabbit cortical vascular smooth muscle cells (RCSMC) and SV-40-transformed human glomerular visceral epithelial cells (HGVEC-SV1). N-[2-(p-bromocinnamylamino)ethyl]- 5-isoquinolinesulfonamide (H-89), a PKA inhibitor, decreased ANF-stimulated cGMP production in RCSMC in a time- and concentration-dependent manner. ANF-stimulated cGMP production was markedly inhibited after prolonged 9- and 18-h incubations with 25 microM H-89 (52 and 65%, respectively) but was not altered after exposure of cells to this agent for 1 h. 1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine and N-(2-[methylamino]ethyl)-5-isoquinolinesulfonamide, protein kinase inhibitors not selective for PKA, did not reproduce the effect of H-89, even at higher concentrations (50 and 100 microM). Cycloheximide (10 microM), a protein synthesis inhibitor, limited the inhibitory effect of H-89, although alone it did not modify the ANF-stimulated cGMP production. H-89 did not affect cGMP production when it was stimulated by SIN-1, a nitric oxide donor. Prolonged incubation (18 h) with 8-bromo cAMP or cholera toxin, an activator of Gs protein resulting in adenylate cyclase stimulation, enhanced ANF-dependent cGMP production by 225 and 176%, respectively. This stimulatory effect was blocked by 25 microM H-89. 125I-ANF binding to RCSMC at 4 degrees C was not affected by preincubation of the cells with H-89. There was a 44% decrease in the expression of ANF C receptors measured as the ANF-(4-23)-displaceable 125I-ANF binding at 37 degrees C, which could not, however, explain the inhibitory effect of H-89 on cGMP production. Modulation of ANF- and C-type natriuretic peptide-dependent cGMP production by H-89 and cholera toxin was also found in HGVEC-SV1 with the same characteristics as in RCSMC. Taken together, these results suggest that PKA activity controls the function of natriuretic peptide guanylate cyclase-coupled receptors in the two cell types studied. PKA-dependent inhibition of a negatively regulatory protein distinct from the receptor itself seems necessary for a full cGMP response.

Animals↗
PubMed1997

EGF and TGF-beta regulate neutral endopeptidase expression in renal vascular smooth muscle cells.

We recently reported that neutral endopeptidase (NEP) expression on renal vascular smooth muscle cells (VSMC) was downregulated in the presence of serum. Here we examine the role of epidermal growth factor (EGF) and transforming growth factor-beta 1 (TGF-beta) in this downregulation and the consequences of the changes in NEP activity on their mitogenic effects. EGF inhibited NEP activity, whereas TGF-beta was stimulatory. Expression of the enzyme was studied by measuring the binding of [125I]RB-104, a specific NEP inhibitor, and the fluorescence intensity of NEP-labeled cells. Both parameters were decreased by EGF and were increased by TGF-beta. NEP mRNA expression in EGF-treated cells was reduced after 48 h. In contrast, it was increased in TGF-beta-treated cells. Interestingly, NEP inhibition influenced the mitogenic effect of EGF. Indeed, thiorphan, an NEP inhibitor, and an anti-NEP antibody decreased EGF-dependent [3H]thymidine incorporation and cell proliferation by approximately 50%. TGF-beta had no effect on VSMC growth. These results indicate that EGF but not TGF-beta participates in the downregulatory potency of serum on NEP expression in VSMC. They also demonstrate that the full effect of EGF on VSMC proliferation depends on intact NEP activity.

Animals↗
PubMed1997

[Response of the coronary arteries to cold test and flow velocity increase is improved by deferoxamine but not by L-arginine in diabetic patients].

UNLABELLED: Acetylcholine produces coronary artery (CA) constriction in diabetic patients suggesting an impairment of endothelium-dependent dilation. To examine the mechanism of this abnormal response. 2 physiological tests, i.e. cold pressor test (CPT) and coronary flow-increase induced by 10 mg papaverine (PAP) injection in the distal left anterior descending CA (dLAD), were performed before (1) and after (2) either i.v. L-arginine (L-arg, 625 mg/min x 10 min) or i.v. desferrioxamine (DFX, 50 mg/min x 10 min) in 15 normotensive nonsmoker diabetic patients with angiographically normal CA and normal cholesterol. Dimensions of the proximal LAD (pLAD) were measured by quantitative angiography. [table: see text] Before administration of L-arg or DFX, CPT induced a decrease of pLAD diameter, and PAP injection in dLAD dit not modify pLAD diameter. In the 7 diabetic patients receiving L-arg, responses to CPT and PAP were not modified. Conversely in the 10 patients receiving DFX, pLAD dilated in response to the 2 tests. Intracoronary isosorbide dinitrate, an endothelium-independent dilator, produced similar dilation in the 2 groups (+20 +/- 8% and +16 +/- 6%, respectively). CONCLUSIONS: 1) responses of angiography normal CA to CPT and to flow increase are impaired in diabetic patients; 2) abnormal responses are not improved by L-arg suggesting that a deficit in substrate for NO synthesis is not involved; 3) DFX restores a vasodilator response to the 2 tests suggesting that inactivation of NO by superoxide radicals might be partly responsible of the impairment of CA dilatation in diabetic patients.

Arginine↗
PubMed1996

Interest and limits of in vitro studies in renal vascular endocrinology.

Various in vitro preparations have been utilized to study the cellular activity of vasoactive agents on renal cortical microvessels and on mesangial cells. The receptors and the transduction pathways of bradykinin and atrial natriuretic factor were characterized on cultured cortical vascular smooth muscle cells from the rabbit kidney. A preparation of afferent arterioles that had been freshly isolated from the rat kidney was used to study the NO-dependent regulation of renin release. The influence of endothelin and angiotensin II on mesangial cell proliferation was evaluated, using cocultures of human endothelial and mesangial cells. These appropriate in vitro preparations have provided new insights on renal vascular endocrinology. However, extrapolation of in vitro data to in vivo physiology must be cautious because the phenotype of vascular cells often changes in culture conditions.

Animals↗
PubMed1995

Polymerase chain reaction quantification of lymphoid amyloid precursor protein mRNAs in Alzheimer's disease and Down's syndrome.

Amyloid beta-protein, the major constituent of Alzheimer's disease (AD) brain amyloid deposits, is encoded by several alternatively spliced amyloid precursor protein (APP) mRNAs. The well-established associated in Down's syndrome (DS) between APP overproduction and premature development of AD, as well as the recent demonstration of an increase in APP transcripts from lymphoblastoid cells of familial AD cases, suggest aberrant transcriptional regulation of some genes in AD. We assayed steady-state expression of the APP gene transcripts in peripheral blood mononuclear cells (PBMC) of AD and DS patients using quantitative polymerase chain reaction of reverse-transcribed mRNAs, and we compared their levels of PBMC APP expression with those of young and age-matched healthy controls. Results indicate APP mRNAs were of comparable abundance in PBMC obtained from 9 AD patients, 7 young controls and 12 age-matched controls. These data suggest regulation of APP mRNAs is normal in AD and DS PBMC.

Adult↗
PubMed1995

[Strategies of early reperfusion in acute myocardial infarction].

PURPOSE: To describe the use of myocardial reperfusion strategies (percutaneous transluminal coronary angioplasty-PTCA and intravenous trombolysis) whenever it is possible to use emergency cinecoronariography in acute myocardial infarction (AMI). METHODS: The records of patients admitted with initial diagnosis of AMI, until six hours after the beginning of symptoms, were reviewed retrospectively, between March/92 and December/93. RESULTS: One hundred forty-three patients were admitted with suspected AMI. Eighty-one (57%) presented definitive criteria for this diagnosis. Fifty-two patients (64%) were admitted in the first six hours from the beginning of symptoms. Thirty-eight (73%) were male and the mean age was 59 +/- 12 years. Cinecoronariography was indicated immediately in 36 of 52 (69%) patients, with purpose to use PTCA. That was done in 30 (58%). Two (4%) patients were submitted to emergency surgical myocardial revascularization. Intravenous thrombolysis was used in 11 (21%) patients. At admission, the conservative treatment was chosen for five out of nine left patients, based on clinical grounds. CONCLUSION: The availability of emergency cinecoronariography made an early reperfusion strategy possible in 83% of patients admitted with AMI in the first six hours after the beginning of symptoms.

Angioplasty, Balloon, Coronary↗
PubMed1994

Amyloid precursor protein gene expression in neural cell lines: influence of DNA cytosine methylation.

Transcription of the gene encoding amyloid precursor protein (APP) varies in a cell-specific and developmentally regulated manner. The 5' region of this gene possesses a high frequency of CpG dinucleotides as well as copies of a GC-rich sequence, a potential trans factor binding element. These findings raise the possibility that DNA cytosine methylation could participate in the regulation of APP gene expression. We examined APP mRNA/18S rRNA ratio in three neural cell lines (N18TG2, SN6, SN17) cultured in 5-azacytidine (5-AZA), an inhibitor of maintenance methylase which results in loss of cytosine methylation in proliferating cells. Culture in 5-AZA globally reduced methylation in genomic DNA as assessed by an increase in HpaII restriction sites, reduced cytosine methylation in the APP gene as assessed by Southern blotting of HpaII digests, and increased APP mRNA steady state abundance in all studied cell lines. Cell lines re-acquired APP gene methylation 48 h after removal of 5-AZA from media. These results indicate that in vitro alteration of DNA methylation can affect APP gene expression, and suggest that the APP gene in neuronal cell lines may be rapidly inactivated in vitro, perhaps to neutralize its potential toxicity.

Amyloid beta-Protein Precursor↗
PubMed1994

Self-reported use of drugs for sleep or distress among French adolescents.

PURPOSE: In the framework of an epidemiological survey on adolescent health, we investigated teenagers' psychotropic drug use to identify risk factors. METHODS: A representative sample of school adolescents aged 12-20 years (N = 3287) was asked to fill out a self-administered questionnaire on their current health status (depressive mood, somatic complaints) and their psychotropic drug use. Parents completed a second questionnaire about the subjects' childhood. RESULTS: About one in five (21.1%) indicated having used psychotropic medications during the previous 12 months, most of which were prescription drugs. Drugs for tension or distress were taken more frequently than ones for sleep disorders. Psychotropic drug use was more widespread among girls (27.5%) than among boys (13.8%), and it increased with age: at 18 years 27.9% of the teenagers (versus 12.7% at age 12-13 years) had used psychotropic medicine. Adolescent psychotropic drug use was related to current depressive mood or somatic complaints, and to consumption of psychotropic drugs during childhood. A logistic regression analysis showed that current depression and past psychotropic use between the ages of 6-12 years were the major associated factors of adolescent consumption. CONCLUSIONS: The hypothesis of psychotropic drug use as an early "learned" response to psychological problems is discussed.

Adolescent↗
PubMed1994

[Psychotropic drug use in adolescence: why more girls? Study of a sample of 12-20-year-old students in Haute-Marne (France)].

As part of a cross-sectional survey on adolescent health, psychotropic drug use was investigated by a self-administered questionnaire on school based adolescents aged 12-20 years (N = 3,279). 27.5% of the girls and 13.8% of the boys had taken a psychotropic drug during the 12 previous months. Female overuse was observed for different types of drugs (for distress/anxiety, sleep disturbance...) whether prescribed or not. Increased use with age was more marked for girls (14.3% to 36.2%) than for boys (10.7 to 16.9%). Psychotropic drug use increased with depressiveness, somatic complaints and medical care. A logistic regression analysis showed that female consumption was still slightly higher than that of boys after adjustment on other related factors.

Adolescent↗
PubMed1993

The C. elegans cell death gene ced-3 encodes a protein similar to mammalian interleukin-1 beta-converting enzyme.

We have cloned the C. elegans cell death gene ced-3. A ced-3 transcript is most abundant during embryogenesis, the stage during which most programmed cell deaths occur. The predicted CED-3 protein shows similarity to human and murine interleukin-1 beta-converting enzyme and to the product of the mouse nedd-2 gene, which is expressed in the embryonic brain. The sequences of 12 ced-3 mutations as well as the sequences of ced-3 genes from two related nematode species identify sites of potential functional importance. We propose that the CED-3 protein acts as a cysteine protease in the initiation of programmed cell death in C. elegans and that cysteine proteases also function in programmed cell death in mammals.

Amino Acid Sequence↗
PubMed1993

Acute and delayed hormonal changes in mitral stenosis treated by balloon valvulotomy.

The role of left atrial and aortic pressures on the secretion of the main hormones controlling blood volume is still subject to debate in humans. Because of increased mean left atrial pressure and decreased mean aortic pressure produced by balloon inflation in patients with mitral stenosis treated with balloon valvulotomy, the hormonal changes occurring acutely (group II of patients) were measured. The same studies (group I patients) were also performed 48 hours after this treatment, a period at which left atrial pressure permanently diminished. Inflation of the balloon resulted in a decrease in plasma renin activity and increases in plasma atrial natriuretic factor (ANF) and plasma arginine vasopressin (AVP). Forty-eight hours after balloon valvulotomy, which had produced a decrease in left atrial pressure, plasma ANF was lower (58.9 +/- 7.9 vs 95.3 +/- 11.9 pg/ml; p < 0.001), and plasma renin activity (2,575 +/- 533 vs 960 +/- 113 pg/ml/hour; p < 0.01), plasma angiotensin II (25.0 +/- 4.1 vs 9.3 +/- 1.3 pg/ml; p < 0.001) and plasma aldosterone (181.7 +/- 36.7 vs 139.9 +/- 19.8 pg/ml; p < 0.05) were higher than their respective control levels 24 hours before treatment of the stenosis. In contrast, plasma AVP (3.7 +/- 0.25 vs 4.4 +/- 0.31 pg/ml; p = 0.001) diminished moderately along with plasma osmolality (282.4 +/- 0.1 vs 286.2 +/- 0.6 mOsm/kg; p < 0.001). Urinary sodium excretion was also examined before and after balloon valvulotomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Amyloid precursor protein in peripheral mononuclear cells is up-regulated with cell activation.

The deposition of beta/A4 protein in extraneural organs of patients with Alzheimer disease suggests that this peptide may in part be derived from a peripheral precursor. We studied expression of amyloid precursor protein (APP) in PBMC. APP expression was detectable in resting PBMC by northern blot analysis, immunoblotting studies, and immunohistochemistry. By reverse transcription-polymerase chain reaction, the 751 and 770 APP transcripts containing the Kunitz protease inhibitor (KPI) domain were approximately 10-fold more abundant than the 695 transcript lacking the KPI domain. Activation of PBMC with the lectin PHA-P was associated with an increase in apparent intracellular APP content by cytofluorometry, and an increase in the proportion of the 695 APP transcript lacking the KPI domain. We conclude that resting and activated PBMC express APP and could contribute to a circulating pool of this protein. In addition, PBMC APP is up-regulated with mitogenic stimulation and may participate in the regulation of activation of these cells.

Alternative Splicing↗